Estimation of the epileptogenic-zone with HFO sub-groups exhibiting various levels of epileptogenicity*

High-Frequency-Oscillations (HFO) are biomarkers of the epileptogenic-zone (EZ) and thus a potential aid in guiding epilepsy-surgery. HFO are normally sub-divided according to their oscillating-frequency into Ripples (80-250 Hz) and Fast-Ripples (FR) (250-500 Hz) and are known to also occur in the non-epileptic brain. We address two challenges faced by HFO: firstly, estimating the margins of the EZ using the HFO occurrence-rate from each intracranial EEG channel; secondly, selecting HFO sub-groups with a higher probability of being purely epileptic. We propose the clustering of channels with high HFO occurrence-rates as a deterministic method to delimit the EZ. Additionally, we perform the EZ estimation using 9 sub-groups of HFO; these sub-groups are determined by their temporal and spatial coincidence with intracranial interictal-epileptic-spikes (IES) and are assumed to have varying levels of epileptogenicity. The EZ estimated with the different HFO-sub-groups are compared between themselves and with a proxy of the factually undefinable EZ, namely the resected-volume (RV). The proposed clustering method proved to be deterministic and allowed estimating the EZ for each patient and each HFO-sub-group. Those Ripples assumed to be more epileptogenic occurred in lower numbers than all Ripples but showed the highest correspondence with the RV. All FR sub-groups showed a high specificity to the RV. The proposed clustering method successfully extracted the information from the HFO occurrence-rate to estimate the EZ. The selection of more epileptogenic HFO based on their coincidence with IES proved to be of value for both Ripples and FR.

[1]  F. Dudek,et al.  Interictal spikes: Harbingers or causes of epilepsy? , 2011, Neuroscience Letters.

[2]  Ayako Ochi,et al.  Focal resection of fast ripples on extraoperative intracranial EEG improves seizure outcome in pediatric epilepsy , 2011, Epilepsia.

[3]  Stephen V. Gliske,et al.  Universal automated high frequency oscillation detector for real-time, long term EEG , 2016, Clinical Neurophysiology.

[4]  Andreas Schulze-Bonhage,et al.  Physiological Ripples Associated with Sleep Spindles Differ in Waveform Morphology from Epileptic Ripples , 2017, Int. J. Neural Syst..

[5]  D. Barth,et al.  Submillisecond Synchronization of Fast Electrical Oscillations in Neocortex , 2003, The Journal of Neuroscience.

[6]  Charles L. Wilson,et al.  High‐frequency oscillations in human brain , 1999, Hippocampus.

[7]  S. P. Lloyd,et al.  Least squares quantization in PCM , 1982, IEEE Trans. Inf. Theory.

[8]  Yahya Aghakhani,et al.  Interrater reliability of visually evaluated high frequency oscillations , 2017, Clinical Neurophysiology.

[9]  J. Sarnthein,et al.  Human Intracranial High Frequency Oscillations (HFOs) Detected by Automatic Time-Frequency Analysis , 2014, PloS one.

[10]  Jiaqing Yan,et al.  Determining the Quantitative Threshold of High-Frequency Oscillation Distribution to Delineate the Epileptogenic Zone by Automated Detection , 2018, Front. Neurol..

[11]  J. Jacobs,et al.  High-frequency oscillations in epilepsy and surgical outcome. A meta-analysis , 2015, Front. Hum. Neurosci..

[12]  D. Thurman,et al.  Estimating Prevalence, Incidence, and Disease‐related Mortality for Patients with Epilepsy in Managed Care Organizations , 2005, Epilepsia.

[13]  Jeffrey A. Loeb,et al.  High inter-reviewer variability of spike detection on intracranial EEG addressed by an automated multi-channel algorithm , 2012, Clinical Neurophysiology.

[14]  Oren Sagher,et al.  Variability in the location of high frequency oscillations during prolonged intracranial EEG recordings , 2018, Nature Communications.

[15]  Andreas Schulze-Bonhage,et al.  Removing high-frequency oscillations , 2018, Neurology.

[16]  J. R. Landis,et al.  The measurement of observer agreement for categorical data. , 1977, Biometrics.

[17]  W T Blume,et al.  A randomized, controlled trial of surgery for temporal-lobe epilepsy. , 2001, The New England journal of medicine.

[18]  J. Born,et al.  About sleep's role in memory. , 2013, Physiological reviews.